Foronjy Robert, D'Armiento Jeanine
Columbia University Medical Center, Divisions of Molecular Medicine and Pulmonary and Critical Care Medicine, New York, New York 10032.
Clin Appl Immunol Rev. 2006 Jan 1;6(1):53-72. doi: 10.1016/j.cair.2006.04.002.
The inhalation of cigarette smoke triggers a marked cellular influx in the lung and this inflammation is believed to play a central role in the development of smoke-related lung diseases such as asthma and COPD. Studies demonstrate that smoke-derived oxidants are a major factor in this inflammatory reaction to cigarette smoke. These oxidants can overwhelm the lung's antioxidant defenses and they can up regulate inflammation by a number of mechanisms. Free radicals directly stimulate the production of chemotactic compounds such as 8-isoprostane. In addition, smoke-derived oxidants can activate several intracellular signaling cascades including NF-κB, MAPK and AP-1. This transcriptional activation induces the expression of cytokines and intracellular adhesion molecules that facilitates the trafficking of neutrophils, macrophages and lymphocytes into the lung. Moreover, oxidants can promote chromatin remodeling that facilitates the expression of proinflammatory genes by stimulating the acetylation of histone residues in the nucleosome. This leads to conformational changes that enhance expression by rendering the gene more accessible to binding to transcriptional factors. Thus, the oxidant-antioxidant imbalance generated by cigarette smoke can promote inflammation which is critical to the functional decline that occurs in both asthma and COPD patients. Future research is needed to better define the effects of smoke-derived oxidants on lung inflammation and to determine the most efficacious strategies for generating significant antioxidant protection in the lung.
吸入香烟烟雾会引发肺部明显的细胞流入，这种炎症被认为在与烟雾相关的肺部疾病（如哮喘和慢性阻塞性肺疾病）的发展中起核心作用。研究表明，烟雾衍生的氧化剂是对香烟烟雾这种炎症反应的主要因素。这些氧化剂会使肺部的抗氧化防御系统不堪重负，并可通过多种机制上调炎症反应。自由基直接刺激趋化性化合物（如8-异前列腺素）的产生。此外，烟雾衍生的氧化剂可激活多种细胞内信号级联反应，包括核因子-κB、丝裂原活化蛋白激酶和活化蛋白-1。这种转录激活诱导细胞因子和细胞内黏附分子的表达，从而促进中性粒细胞、巨噬细胞和淋巴细胞向肺部的迁移。此外，氧化剂可促进染色质重塑，通过刺激核小体中组蛋白残基的乙酰化来促进促炎基因的表达。这会导致构象变化，通过使基因更易于与转录因子结合来增强表达。因此，香烟烟雾产生的氧化剂-抗氧化剂失衡可促进炎症，这对哮喘和慢性阻塞性肺疾病患者出现的功能衰退至关重要。未来需要开展更多研究，以更好地确定烟雾衍生的氧化剂对肺部炎症的影响，并确定在肺部产生显著抗氧化保护作用的最有效策略。
